Mortality associated with intestinal perforation

caused by NEC and treated with primary laparotomy remains at about 40% in premature infants with a birth
weight less than 1,000 g and about 50% in those under
750 g.6-8,13-16 The combined effects of general anesthesia
and major abdominal surgery increase the risk of hemodynamic
instability caused by hypotension, transfusion
requirements, third spacing of fluids, and hypothermia.
Furthermore, intestinal ischemia secondary to local vasoconstrictive
effects and visceral shunting (diving reflex)
might be triggered leading to infarction.8
This prospective multicentered trial was performed
after a treatment algorithm (Fig 1), and the results was
compared with a historical control group (Tables 6,7).
We have divided our patients according to indication
of PD (group 1, pneumoperitoneum or group 2, peritonitis)
and weight less than or greater than 1,000 g with
the aim of comparing the results with those of other
reports.
In our series 24 infants (64%) survived after only PD, 8 (80%) in group 1, and 16 (89%) in group 2. Eleven
infants (48%) survived after only PD with birth weight
less than 1,000 g. This means that approximately half of
the infants, regardless of weight and gestational age,
survived from severe NEC and PD. However, more than
half of them (54%) required delayed surgery because of
intestinal complications (stenosis, fistula, strictures) but
always in a more favorable clinical condition, without
severe intestinal sequela. However, as reported previously,
17 these type of intestinal complications are seen
more frequently in infants with advanced NEC treated
with PD than after laparotomy. In our series, none of
those infants who survived after PD plus laparotomy
needed delayed surgery.
About 36% needed laparotomy after PD because of
clinical worsening or not enough improvement. The
results were extremely poor in infants under 1,000 g at
birth and pneumoperitoneum (all 4 infants died), and in
infants under 1,000 g and peritonitis only 50% survived.
However, in infants with birth weight over 1,000 g the
results were outstanding: 100% survived in group 1 after
only PD or PD plus laparotomy. In group 2, only one
infant died after peritonitis and PD (survival rate 93%).
These results are in disagreement with those reported by Azarow et al7 who found a higher survival rate with
primary laparotomy in newborns with NEC perforation
who weighed more than 1,000 g versus PD and advised
its use only in infants with very low birth weight (less
1,000 g). Higher survival rates in our prospective series
is perhaps caused by use of PD in all infants, not only in
those with perforation as in retrospective studies.
In our series, 10 of 11 infants who died weighed less
than 1,000 g at birth, and their GA was less than 28
weeks; this was the population with the highest neonatal
mortality risk.7 Moreover, if we observe only the overall
mortality rate in infants under 1,000 g at birth, without a
careful study of the mortality causes, we do not really
evaluate the true efficacy of PD. We found that 86% of
the infants improved after PD, with similar percentages
in all studied groups according to the indications of PD
or birth weight. Rovin et al9 also reported a 100%
improvement after PD. When the main cause of mortality
was analyzed, we observed that it was massive NEC (5
of 11) in infants less than 1,000 g at birth. However, in indicated when clinical stabilization was obtained. We
are in agreement with Ataken et al18 in considering it
necessary to have diagnostic criteria to identify those
infants in whom only PD may be sufficient; however,
definite surgical treatment must not be delayed when
clinical stabilization is achieved. In the remaining 3
infants, all with peritonitis caused by massive NEC,
laparotomy was not successful, but there are no reports
with successful results in massive NEC.7,9,15,19-21 In such
cases, laparotomy generally is associated with extensive
intestinal resections with poor outcome7,14; an early PD
and wait-and-see attitude may be better.22 Sonntag et al23
proposes that the prognostic value of multisystem organ
failure and capillary leak syndrome is higher than that of
the classification criteria in NEC of very low birth weight
by Walsh and Kliegman.12 We want to underline that in
the 3 infants with birth weight less than 1,000 g who
died, support was withdrawn, and one of them died after
intestinal function was restored completely.
A very important aspect in our series is the absence of
severe intestinal sequela in our infants with pneumoperitoneum
or weight less than 1,000 g at birth, in contrast
with other reports.14,24 Moreover, we found that in infants
over 1,000 g at birth, only one of them had a short
bowel syndrome; in such situations, to perform a laparotomy
on a highly hemodynamically unstable infant
leads to unfavorable results.22
We began to perform PD in infants with advanced
NEC and peritonitis because we had previously seen
infants with large intestinal necrosis on laparotomy who
did not have pneumoperitoneum. Kazez et al25 showed
that intestinal distension increased the damaging effects
of hypoxia-reoxygenation on the gut. Therefore, we
performed PD when abdominal distension appeared and
peritoneal fluid increased on radiologic examination suggesting
advanced NEC. It is in this group of infants, it is
more difficult to determine when more aggressive therapy
is indicated. We believe that PD is an easy procedure
with minimal risk. Neonatologists and pediatric surgeons
must diagnose and treat these problems sooner before
impairment progresses, taking into account the wide
variability in interpretation of abdominal radiographs of
infants with suspected NEC.26
Current evidence suggests that the immature neonatal
gut barrier may be particularly susceptible to splanchnic
hypoperfusion. Perinatal insults that impair mesenteric
circulation may, therefore, induce intestinal mucosal injury
and permit local intestinal microbial flora to breach
the mucosal barrier. This process, in turn, initiates an
inflammatory cascade leading to full-blown NEC.27,28
Edelson et al29 describes that interleukin-8 (IL-8); IL-1
receptor antagonist (IL-1ra), and IL-10 are released more
slowly after such a stimulus and may be more useful than IL-6 or tumor necrosis factor alpha (TNF _) to
identify
more severe cases earlier. However, the role of inflammatory
cytokines and nitric oxide in the pathogenesis of
NEC still is undefined.30 Therefore, if we can identify,
within hours of onset of symptoms, which babies have
bowel damage, this treatment (PD) can be initiated earlier.
Furthermore, Lessin et al8 proposed PD followed by
irrigation with normal saline solution until the fluid
drained is clear, and Birk et al31 included the use of a
continuous lavage system for postoperative treatment to
eliminate endotoxines and cytokines.
We want to point out another aspect of confusion in 3
infants who had pneumoperitoneum caused by something
other than NEC (intestinal perforation from Meckel’s
diverticulum and intestinal duplication, appendicitis
and Hirschsprung’s disease); all 3 patients had overwhelming
sepsis, and it was not indicated to perform
laparotomy because of their severe instability. All 3
infants survived after PD, and surgery was performed
some days later when their clinical condition was appropriate.
Therefore, we suggest performing PD as an emergency
on any infant with pneumoperitoneum or massive
abdominal distension and suspected of having some risk of
mesenteric blood-flow impaired, especially anyone who
needs to be transported to another hospital for surgery.
From data obtained from retrospective studies, there is
no unanimous evidence that PD or primary laparotomy is
better in treating advanced NEC, especially in the tiniest
babies.32 Richter33 noted that Moss et al33 have begun a
prospective, controlled and randomized trial that may
clear the air, however, there are many variables that may
make any study difficult. Perhaps, as Ehrlich et al recently
reported34, “the outcome of perforated NEC may be independent
of the type of surgical treatment,” and he suggests
that selection of therapeutic options for the patient requires
evaluating all comorbid factors that may impact survival,
rather than applying a single treatment strategy for all
patients.
The results obtained in this prospective study suggest
that an early and primary peritoneal drainage is not a
definitive solution in all patients, but are not poor compared
with results obtained in the historical control with
primary laparotomy, many infants survived without need
surgery, and the number of infants with severe intestinal
sequela are decreased.

Treatment NEC medis dan pembedahan15

Surgical management
A proportion of medically managed infants with necrotizing enterocolitis
require acute surgical intervention, due to clinical deterioration
or intestinal perforation. Whilst the latter indication is clearly
identified with radiologic evidence of pneumoperitoneum, signs of
clinical deterioration leading to surgery can be more subtle. These
include requirement of inotropes, worsening abdominal findings,
hemodynamic instability, worsening laboratory values (intractable
acidosis, persistent thrombocytopenia, rising leukocytosis, or worsening
leukopenia), and/or sonographic evidence of decreased or
absent bowel perfusion.
A laparotomy in high-risk neonates, especially if born with an
extremely low weight, can result in serious morbidity or even
mortality. To avoid this risk, in 1977 Ein et al. first described the
percutaneous insertion of a peritoneal drain in five neonates with
bowel perforation as a temporizing measure to delay laparotomy 50.
The authors noticed a clinical improvement of these infants within week, so that they advocated the peritoneal drainage of
small
infants with perforated necrotizing enterocolitis. In support of this
approach, a few years later, the same authors published a bigger
series where they showed that 40% of neonates <1500 g treated with
the peritoneal drain had complete resolution of their disease without
requiring further surgery51. A similar experience with the peritoneal
drain was later reported by other authors52–54. However, this
surgical approach has been very controversial and two prospective
randomized controlled trials comparing the use of peritoneal drain
vs. laparotomy in infants with perforated necrotizing enterocolitis
were carried out55,56. Interestingly, neither of the two trials was able
to demonstrate an advantage of one treatment modality over the
other55,56. Moreover, Rees et al. demonstrated that in neonates with
<1000 g body weight and perforated necrotizing enterocolitis, peritoneal
drainage was not a definitively effective procedure, as 74%
of the infants required a rescue laparotomy57. It is still debatable
whether there is a role for peritoneal drainage in the stabilization
of a critically unwell child with perforated necrotizing enterocolitis
and/or respiratory compromise, prior to the transfer to another
center for laparotomy57.
The universal principles of surgery in necrotizing enterocolitis are
to remove the necrotic intestine and control intra-abdominal sepsis
while preserving as much intestinal length as possible57. Within
these principles, there are different surgical options that surgeons
favor on the basis of personal experience, rather than evidencebased
literature58. The classical approach to necrotizing enterocolitis
has been to resect all areas of the necrotic intestine and fashion
a stoma to allow adequate time for healing and growth before
restoring intestinal continuity at a later stage. However, stomas,
and in particular jejunostomies, are poorly tolerated by preterm
infants, as they predispose them to nutritional and metabolic disturbances
and poor growth as a consequence of fluid and electrolyte
depletion47. Therefore, some surgeons would resect necrotic bowel
and perform a primary anastomosis, even in neonates weighing less
than 1000 g58. To investigate which is the most effective operation
for neonates with surgical necrotizing enterocolitis, a multicenter
randomized controlled trial of resection with primary anastomosis
vs. resection with stoma (STAT: Stoma or Intestinal Anastomosis
Trial) is currently underway.
Moreover, there is no consensus among surgeons on the type of
stoma to fashion and where to locate it with regard to the surgical
wound58. This is in line with the outcomes of a recent systematic
review of the literature that showed no difference in the type or
location of colostomy in children with colorectal disease 59.
At laparotomy, some infants are found to have multifocal necrotizing
enterocolitis and require multiple resections and multiple
anastomoses. In 1996, Vaughan et al. described an alternative
approach for such cases: the “clip-and-drop” technique 60. According
to this technique, the multiple necrotic areas are resected, the
bowel ends are sealed with titanium clips or staples, and the clipped
bowel loops are returned to the abdominal cavity. At a second-look
laparotomy, the bowel loops can be reassessed and anastomoses can
be performed. Since the first description, the “clip-and-drop” technique
has been employed for infants with multifocal necrotizing
enterocolitis by other authors60–62. When the vast majority of the intestine is affected by severe intestinal
damage, the patient is considered to have pancolitis or NEC
totalis. This is a very controversial scenario, as the resection of the
necrotic bowel may involve almost the whole intestine. Options
include closing the abdomen and withdrawing care, or creating a
diverting jejunostomy. The latter has been described to rescue a
proportion of neonates with extensive necrotizing enterocolitis and
to result in enteral autonomy in most patients63.

Treatment Pembedahan NEC14

Teknik Clip and drop sesuai dengan prinsip pembedahan, juga mencegah pembentukan
stroma. Vaughan et al.
For the infant with
extensive bowel necrosis, Vaughan et al. [41]
advocated the resection of all segments of grossly
nonviable or perforated bowel, irrigation and
aspiration of peritoneal contamination, clipping
the ends of remaining bowel and returning them
to the abdomen. This is followed by a second-look
laparotomy with delayed anastomosis 48—72 h
later. In their small series, all three infants with
NEC survived [41] and in a subsequent report of
four infants in whom this technique was employed,
one died and the remaining three required stoma
formation at the second look. This technique has
the advantages of preserving bowel length and
intends to avoid stoma formation.

5. Author’s preferred surgical approach

The author’s preferred approach to the surgical
management of the disease is illustrated in Fig. 1.
In the presence of clear indications for surgery, a
laparotomy is performed in infants N1000 g. In very
small infants b1000 g, the use of primary peritoneal
drainage is considered. When the indication
for surgery is unclear, diagnostic laparoscopy is
used to exclude intestinal perforation or intestinal
gangrene.
Resection and primary anastomosis is usually
performed in stable infants with focal and multifocal
disease when it is possible to ascertain the viability of the bowel distal to NEC without causing
significant bleeding. A stoma (with or without
intestinal resection) is performed when: (a) it is
not possible to ascertain the status of the bowel
distal to the NEC; (b) the distal bowel is of dubious
viability; (c) attempts to dissect the distal bowel
cause significant bleeding; (d) the patient is unstable
peri-operatively. In patients with pan-intestinal
disease (N75% of small and large bowel involved)
two options are considered: (a) proximal diverting
jejunostomy when the intestinal resection would
cause significant bleeding or loss of the majority of
the small bowel; (b) bclip and dropQ technique in the
attempt to salvage some of the affected bowel and
avoid a short bowel syndrome. In neonates with
gangrene of the entire small bowel, the abdomen is
closed and treatment is withdrawn.